miR-17-3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition.

Abstract

Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR-17-3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR-17-3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR-17-3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR-17-3p might be a diagnostic index of MM. Moreover, miR-17-3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR-17-3p. Negatively regulated by miR-17-3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR-17-3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR-17-3p-LMLN-P21 axis in MM progression.

• Authors: Pu Xiang, Yiu To Yeung, Jiheng Wang, Qiong Wu, Ruijuan Du, Chuntian Huang, Xuechao Jia, Yunfeng Gao, Yafei Zhi, Fangqin Guo, Huifang Wei, Dandan Zhang, Yuzhang Liu, Lina Liu, Lijie Liang, Juan Wang, Yongping Song, Kangdong Liu, Baijun Fang
• Journal: International journal of cancer (Int J Cancer) Vol. 148 Issue 12 Pg. 3071-3085 (06 15 2021) ISSN: 1097-0215 [Electronic] United States
• PMID: 33609405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• MIRN17 microRNA, human
• MicroRNAs
• Metalloendopeptidases
• invadolysin, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Metalloendopeptidases (genetics, metabolism)
• Mice
• MicroRNAs (genetics)
• Middle Aged
• Multiple Myeloma (genetics, metabolism, pathology)
• Neoplasm Transplantation
• Up-Regulation